@article{oai:repo.qst.go.jp:00048414,
 author = {Yoshii, Yukie and Yoshimoto, Mitsuyoshi and Matsumoto, Hiroki and Furukawa, Takako and Zhang, Ming-Rong and Inubushi, Masayuki and Tsuji, Atsushi and Fujibayashi, Yasuhisa and Higashi, Tatsuya and Saga, Tsuneo and 吉井 幸恵 and 張 明栄 and 辻 厚至 and 東 達也},
 issue = {54},
 journal = {Oncotarget},
 month = {Sep},
 note = {Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is an
antiangiogenic agent clinically used for various cancers. However, repeated use of
this agent leads to tumor-decreased vascularity and hypoxia with activation of an
HIF-1 signaling pathway, which results in drug delivery deficiency and induction of
malignant behaviors in tumors. Here, we developed a novel strategy to treat tumors
with bevacizumab-induced vascular decrease and hypoxia using 64Cu-diacetyl-bis
(N4-methylthiosemicarbazone) (64Cu-ATSM), a potential theranostic agent, which
possesses high tissue permeability and can target over-reduced conditions under
hypoxia in tumors, with a human colon carcinoma HT-29 tumor-bearing mouse model.
The long-term treatment with bevacizumab caused decreased blood vessel density
and activation of an HIF-1 signaling pathway; increased uptake of 64Cu-ATSM was also
observed despite limited blood vessel density in HT-29 tumors. In vivo high-resolution
SPECT/PET/CT imaging confirmed reduced vascularity and increased proportion of
64Cu-ATSM uptake areas within the bevacizumab-treated tumors. 64Cu-ATSM therapy
was effective to inhibit tumor growth and prolong survival of the bevacizumab-treated
tumor-bearing mice without major adverse effects. In conclusion, 64Cu-ATSM therapy
effectively enhanced anti-tumor effects in tumors with bevacizumab-induced vascular
decrease and hypoxia. 64Cu-ATSM therapy could represent a novel approach as an add-on to antiangiogenic therapy.},
 pages = {88815--88826},
 title = {64Cu-ATSM internal radiotherapy to treat tumors with bevacizumab-induced vascular decrease and hypoxia in human  colon carcinoma xenografts},
 volume = {8},
 year = {2017}
}